Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation

Changbai Sui; Ying Liu; Jun Jiang; Jianhua Tang; Ling Yu; Guoying Lv

Brain Research Bulletin (Oct 2024)

Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation

Changbai Sui,
Ying Liu,
Jun Jiang,
Jianhua Tang,
Ling Yu,
Guoying Lv

Affiliations

Changbai Sui: Department of Neurology, Yantaishan Hospital, Yantai 264001, China
Ying Liu: Department of Neurology, Yantaishan Hospital, Yantai 264001, China
Jun Jiang: Key Laboratory of Genetics Research and Evaluation of the National Drug Administration, Shandong Institute for Food and Drug Control, Shandong, Jinan 250033, China
Jianhua Tang: Department of Neurology, Yantaishan Hospital, Yantai 264001, China
Ling Yu: Department of Neurology, Yantaishan Hospital, Yantai 264001, China
Guoying Lv: Department of Anesthesiology, The Second Hospital， Cheeloo College of Medicine, Shandong University, Jinan 250033, China; Correspondence to: Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, China.

Journal volume & issue: Vol. 216
p. 111043

Abstract

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Objective: This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion. Methods: In this study, we observed the apoptosis of RM cells (microglia) after oxygen-glucose deprivation/reoxygenation (OGD/R) modeling before and after Rg1 administration, changes in mitochondrial membrane potential, changes in the content of Reactive oxygen species (ROS) and inflammatory vesicles NLR Family Pyrin Domain Containing 3 (NLRP3), and the expression levels of autophagy-related proteins, inflammatory factors, and apoptosis proteins. We further examined the pathomorphological changes in brain tissue, neuronal damage, changes in mitochondrial morphology and mitochondrial structure, and the autophagy-related proteins, inflammatory factors, and apoptosis proteins expression levels in CI/RI rats before and after administration of Rg1 in vivo experiments. Results: In vitro experiments showed that Rg1 induced mitochondrial autophagy, decreased mitochondrial membrane potential, and reduced ROS content thereby inhibiting NLRP3 activation, decreasing secretion of inflammatory factors and RM cell apoptosis by regulating the PTEN induced putative kinase 1(Pink1) /Parkin signaling pathway. In vivo experiments showed that Rg1 induced mitochondrial autophagy, inhibited NLRP3 activation, improved inflammatory response, and reduced apoptosis by regulating the Pink1/Parkin signaling pathway, and Rg1 significantly reduced the area of cerebral infarcts, improved the pathological state of brain tissue, and attenuated the neuronal damage, thus improving cerebral ischemia/reperfusion injury in rats. Conclusion: Our results suggest that ginsenoside Rg1 can ameliorate cerebral ischemia-reperfusion injury by modulating Pink1/ Parkin-mediated mitochondrial autophagy in microglia and inhibiting microglial NLRP3 activation.

Published in Brain Research Bulletin

ISSN: 1873-2747 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.sciencedirect.com/journal/brain-research-bulletin

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